Protective Effects of Curcumin and Resveratrol on Neurodegeneration and Cognitive Dysfunction in a Streptozotocin-induced Alzheimer Rat Model

Background: Alzheimer's disease (AD) is a degenerative neurological disorder characterized by progressive impairment of memory, cognition, and behavior. Since current treatment approaches have been unable to significantly slow the progression of the disease, there is an increasing need for new neuroprotective strategies. This study aims to investigate the protective effects of curcumin and resveratrol on neurotoxicity and the resulting cognitive impairments. Methods: A total of 60 male Wistar albino rats were included in the study. On day 1, an experimental Alzheimer’s model was induced by a single intracerebroventricular injection of streptozotocin (STZ) at a dose of 3 mg/kg. Following model induction, the animals were randomly assigned into six groups: Alzheimer’s disease (ALZ) group, ALZ+curcumin (ALZ+CUR) group, ALZ+resveratrol (ALZ+RES) group, ALZ+curcumin+resveratrol (ALZ+CUR+RES) group, SHAM group, and control group. Morris water maze test, open field test and passive avoidance test were used for behavioral tests; GFAP and caspase-3 tests for immunohistochemical analysis; TAS/TOS values for biochemical analysis and Cavalieri method for stereological examination. Results: Behavioral tests demonstrated that curcumin and resveratrol significantly improved neurobehavioral outcomes. Histological analyses revealed that curcumin and resveratrol reduced the density of cells stained with Caspase 3 (+) and glial fibrillary acidic protein (GFAP) (+), thereby alleviating neuronal cell death and astrocyte activation. Stereological analyses demonstrated that curcumin and resveratrol improved the STZ-induced hippocampal volume reduction. Serum levels of Total antioxidative status (TAS) and Total oxidative status (TOS) measured in serum samples indicated that oxidative stress induced by STZ was reduced by curcumin and resveratrol. While these two compounds exhibited neuroprotective effects when administered alone, no such effect was observed when administered together, suggesting that combination therapy did not produce the expected synergistic effect. Conclusion: This study demonstrated that curcumin and resveratrol, when administered alone, reduce oxidative stress and neuroinflammation caused by STZ, prevent neuronal apoptosis, and exhibit significant neuroprotective effects in ALZ, thereby improving learning and memory functions. These findings suggest that curcumin and resveratrol may serve as effective therapeutic agents in the treatment of Alzheimer's disease.